评估子宫内膜癌 ProMisE 分子亚组中的 DNA 倍性。
Assessment of DNA Ploidy in the ProMisE molecular subgroups of endometrial cancer.
机构信息
Department of Gynecology and Obstetrics, University of British Columbia, Vancouver, British Columbia, Canada.
Institute for Cancer Genetics and Informatics, Oslo University Hospital, Oslo, Norway; Centre for Cancer Biomedicine, University of Oslo, Oslo, Norway.
出版信息
Gynecol Oncol. 2017 Sep;146(3):596-602. doi: 10.1016/j.ygyno.2017.06.020. Epub 2017 Jun 21.
OBJECTIVE
We sought to determine whether DNA ploidy correlates with the four molecular subgroups of endometrial carcinoma (EC) as determined using ProMisE (Proactive Molecular Risk Classifier for Endometrial Cancer).
METHODS
90 cases of EC previously characterized by clinicopathological parameters, outcomes, and ProMisE molecular subgroup (POLE EDM, MMR-D, p53 wt or p53 abn) were assessed for DNA ploidy using image cytometry. Associations of ploidy with traditional clinicopathological parameters were also tested.
RESULTS
Abnormal DNA ploidy status differed amongst the ProMisE groups (p<0.001) and was found in 80.9% (17/21) of p53 abn, 37.0% (10/27) of p53 wt, 28.6% (4/14) of POLE EDM and 14.3% (4/28) of MMR-D. Abnormal DNA content was significantly associated with lower BMI (p=0.034) and grade 3 tumors (p=0.001). In the entire cohort, abnormal DNA content was significantly associated with worse progression free survival (p=0.0094) but not disease specific survival (p=0.249) or overall survival (p=0.187). When examining ploidy within each of the ProMisE groups, abnormal DNA content correlated with worse overall survival (p=0.041) and progression free survival (p=0.011) in the MMR-D group. No statistically significant relationship was seen in the remaining 3 groups.
CONCLUSION
Abnormal DNA ploidy status did correlate with the molecular subgroups of EC; abnormal DNA content was seen in the large majority of p53 abn cases. Abnormal ploidy however was also seen in smaller numbers in the p53 wt, POLE EDM and MMR-D groups; therefore abnormal DNA content was not a specific marker for any one molecular group. The addition of ploidy to the ProMisE molecular categories conferred additional prognostic value within the MMR-D group, which merits further study.
目的
我们旨在确定 DNA 倍性是否与使用 ProMisE（子宫内膜癌主动分子风险分类器）确定的子宫内膜癌（EC）的四个分子亚组相关。
方法
90 例 EC 病例先前通过临床病理参数、结果和 ProMisE 分子亚组（POLE EDM、MMR-D、p53wt 或 p53abn）进行了特征描述，使用图像细胞术评估了 DNA 倍性。还测试了倍性与传统临床病理参数的关联。
结果
异常 DNA 倍性状态在 ProMisE 组之间存在差异（p<0.001），在 80.9%（17/21）的 p53abn、37.0%（10/27）的 p53wt、28.6%（4/14）的 POLE EDM 和 14.3%（4/28）的 MMR-D 中发现。异常 DNA 含量与较低的 BMI（p=0.034）和 3 级肿瘤（p=0.001）显著相关。在整个队列中，异常 DNA 含量与无进展生存期（p=0.0094）显著相关，但与疾病特异性生存期（p=0.249）或总生存期（p=0.187）无关。当在每个 ProMisE 组中检查倍性时，异常 DNA 含量与 MMR-D 组的总生存期（p=0.041）和无进展生存期（p=0.011）较差相关。在其余 3 个组中未见统计学上显著的关系。
结论
异常 DNA 倍性状态确实与 EC 的分子亚组相关；在大多数 p53abn 病例中发现了异常 DNA 含量。然而，在 p53wt、POLE EDM 和 MMR-D 组中也发现了较小比例的异常倍性；因此，异常 DNA 含量不是任何一个分子组的特异性标志物。在 MMR-D 组中，将倍性添加到 ProMisE 分子类别中赋予了额外的预后价值，这值得进一步研究。
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